Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, VA Puget Sound Health Care System and University of Washington, Seattle.
Institute of Cardiovascular Science, University College London, London, U.K.
Diabetes Care. 2024 Aug 1;47(8):1350-1359. doi: 10.2337/dc24-0491.
To determine whether semaglutide slows progression of glycemia in people with cardiovascular disease and overweight or obesity but without diabetes.
In a multicenter, double-blind trial, participants aged ≥45 years, with BMI ≥27 kg/m2, and with preexisting cardiovascular disease but without diabetes (HbA1c <6.5%) were randomized to receive subcutaneous semaglutide (2.4 mg weekly) or placebo. Major glycemic outcomes were HbA1c and proportions achieving biochemical normoglycemia (HbA1c <5.7%) and progressing to biochemical diabetes (HbA1c ≥6.5%).
Of 17,604 participants, 8,803 were assigned to semaglutide and 8,801 to placebo. Mean ± SD intervention exposure was 152 ± 56 weeks and follow-up 176 ± 40 weeks. In both treatment arms mean nadir HbA1c for participants was at 20 weeks. Thereafter, HbA1c increased similarly in both arms, with a mean difference of -0.32 percentage points (95% CI -0.33 to -0.30; -3.49 mmol/mol [-3.66 to -3.32]) and with the difference favoring semaglutide throughout the study (P < 0.0001). Body weight plateaued at 65 weeks and was 8.9% lower with semaglutide. At week 156, a greater proportion treated with semaglutide were normoglycemic (69.5% vs. 35.8%; P < 0.0001) and a smaller proportion had biochemical diabetes by week 156 (1.5% vs. 6.9%; P < 0.0001). The number needed to treat was 18.5 to prevent a case of diabetes. Both regression and progression were dependent on glycemia at baseline, with the magnitude of weight reduction important in mediating 24.5% of progression and 27.1% of regression.
In people with preexisting cardiovascular disease and overweight or obesity but without diabetes, long-term semaglutide increases regression to biochemical normoglycemia and reduces progression to biochemical diabetes but does not slow glycemic progression over time.
确定司美格鲁肽是否能延缓伴有心血管疾病和超重或肥胖但无糖尿病的患者的血糖进展。
在一项多中心、双盲试验中，年龄≥45 岁、BMI≥27kg/m2 且患有既往心血管疾病但无糖尿病（HbA1c<6.5%）的参与者被随机分配至接受皮下注射司美格鲁肽（每周 2.4mg）或安慰剂。主要血糖结局为 HbA1c 和达到生化正常血糖（HbA1c<5.7%）和进展为生化糖尿病（HbA1c≥6.5%）的比例。
在 17604 名参与者中，8803 名被分配至司美格鲁肽组，8801 名被分配至安慰剂组。平均（±SD）干预暴露时间为 152±56 周，随访时间为 176±40 周。在治疗组中，参与者的最低 HbA1c 平均值在 20 周时达到。此后，两组的 HbA1c 均呈相似增加，平均差值为-0.32 个百分点（95%CI-0.33 至-0.30；-3.49mmol/mol[-3.66 至-3.32]），且整个研究过程中司美格鲁肽均具有优势（P<0.0001）。体重在 65 周时趋于平稳，司美格鲁肽组降低 8.9%。在第 156 周时，接受司美格鲁肽治疗的患者中，血糖正常的比例更高（69.5% vs. 35.8%；P<0.0001），且在第 156 周时发生生化糖尿病的比例更低（1.5% vs. 6.9%；P<0.0001）。预防 1 例糖尿病的治疗需要人数为 18.5。糖尿病的发生和进展均依赖于基线时的血糖水平，体重减轻的幅度对于介导 24.5%的进展和 27.1%的回归至关重要。
在伴有既往心血管疾病和超重或肥胖但无糖尿病的患者中，长期使用司美格鲁肽可增加生化正常血糖的回归并降低生化糖尿病的进展，但不能随着时间的推移减缓血糖进展。
